The major challenges in biopolymer-based engineering of load-bearing tissues are mechanical- strength and stiffness. In vitro, as in vivo, properties are controlled by composition and architecture, on the nm-mu m scale of the fibril network. The functional scale is much larger, mm-cm. We will create, implement, validate, and disseminate a computational tool to predict functional scale mechanics based on a network-scale model of engineered tissues. The model will use volume-averaging theory to couple across scales, yielding a macroscopic equation set informed by microscopic behavior. The theory allows study of different systems by varying only the microscopic model. Coupling will occur at Gauss points of the macroscopic finite elements. P-adaptivity will be used to optimize distribution of Gauss points, and the software will operate in parallel to meet the computational demands of many microscopic-scale model solves. Experimental validation will be performed by comparison with two systems. Acellular fibrin-collagen co-gels have two distinct, relatively well-characterized networks. Cultured fibrin-based model tissues, in which entrapped smooth-muscle cells have secreted collagen and elastin, will be more difficult to characterize, but they will be a key step towards the goal of a general model of engineered tissue micromechanics. The program announcement identifies three critical expectations: collaboration, scale-bridging, and new understanding. Some of the team members have worked together in the past, but this project is a new link between mechanics, computational science, and tissue engineering. Likewise, it will link the microscopic scale (most easily controlled by the tissue engineer), and the macroscopic scale (needed for tissue performance). The lack of clear understanding of even simple artificial tissues presents an opportunity for major advancement by drawing on the microstructure to describe the material. This project is highly relevant to public health because of the large potential impact of engineered tissue, particularly structural cardiovascular tissue. Many people need replacement arteries or valves, and there are severe flaws with existing options, creating the need for a new generation of artificial tissues. Understanding, predicting, and controlling the mechanical properties of those tissues will be a critical step forward.